1. Field of the Invention
The present invention relates to a method for processing a sensor chip, especially to a method for processing a chip for biological or chemical use wherein longitudinal acoustic waves are employed to remove non-specifically bound adsorbates or interfering adsorbates, as well as to regenerate sites for specifically bound adsorbates or target adsorbates.
2. Description of the Prior Art
Over the past few decades a large increase of research literature about the application of ultrasonic energy can be found in different scientific fields, especially for chemistry and biology. In general, the prior art has indicated that ultrasound facilitates chemical analyses. For example, ultrasound is considered capable of speeding up enzymatic reactions, accelerating measurements by enhancing mass transport, enhancing solid-liquid elemental extraction, as well as using cavitation effects for causing the formation and collapse of liquid micro jet to induce a rapid stirring of the liquid. See: Ultrasound in Chemistry: Analytical Applications (ISBN: 978-3-527-31934-3), Modern Pathology (2005) 18:950-863, and J. Med. Microbiol. (2000) 49:853-859. Other than the aforementioned applications, utilizing ultrasonic waves to manipulate biomolecule specifically further enables numerous potential applications. For instances, it enhances the sensing sensitivity and improves signal-to-noise ratio as described in Int. J. Legal Med (2009) 123:521-525, mixes or separates the particles in microfluidic regime with fast response time as described in Chemical Society Reviews (2007) 36:492-506 and Sensors and Actuators B (2003) 95:425-434, lyses the cells to obtain proteins and DNA as described in Biophysics (2008) 53(3): 250-251 or deposits cells onto the desired location in a biochip as described in Biosensors and Bioelectronics (2004) 19:1021-1028.
As described in Sensors and Actuators B (2007) 121:452-461, it is beneficial to use ultrasonic forces to manipulate bioparticles. Under activation of ultrasonic waves, a force field is generated by the vibrating source that couples the pressure transmitted through a fluidic medium. The force field manipulates biomolecules with a pressure exerted on the whole surfaces of these molecules. Thus, various functions would be achieved. For example, more kinetic energy can be provided to enhance specific molecular binding or to reduce aggregation of non-specific particles. The interaction of reactant and reagent can be more efficient than a diffusion-based reaction. Additionally, compared with other methods for manipulating bioparticles, ultrasound surpasses dielectrophoresis because the electrical properties of the biomolecules and the fluid medium employed are not of major concern. The direct contact force applied by an instrument, for example, a solid tip, may damage the bioparticles. Non-contact force induced by ultrasound is free from the aforementioned damage done by direct contact.
In terms of bioassay usage, non-specific molecular binding can lower the sensitivity of bio-detection because noise suppresses signals. This could be a serious problem and thus removing non-specific molecules that bind to or aggregate at specific detection regions allows effective target-probe interactions and increases the detectable signals from the bindings of target adsorbates and probes. Therefore, sensing enhancement can be achieved by improving the sensitivity, lowering the detection limit, and even reducing the sensing time.
In addition, to regenerate the activity of the immobilized sensing probes after reacting with target adsorbates, or analytes, and then breaking the linkage thereof for repeat usage is also important for biochemical detection. This would be more valuable when dealing with some expensive or rare molecules. Fast and reliable regeneration process could also shorten the time necessary for preparing immobilized probe molecules onto the biosensor substrates, and lessen the adverse effect to the environment due to massive biochips with only one-time usage capability.
To overcome the shortcomings, the present invention provides a method for processing a sensor chip to mitigate or obviate the aforementioned problems.